FY17 Moon Shots Program Annual Report

FISCAL YEAR 2017

MOON SHOTS PROGRAM

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ANNUAL REPORT

Thank you for believing in our mission to end cancer.

As we report back to you, our generous donors, in the fifth year of The University of Texas MD Anderson Cancer Center’s Moon Shots ProgramTM, you will notice two clear themes. First, and most important, we are achieving results. We have opened 180 clinical trials based on Moon ShotsTM-generated research, and the projects we initiated at the launch of this ambitious program are benefiting patients in our clinics as well as people in our communities. The Anderson Algorithm is improving prospects for women with ovarian cancer and is being replicated by medical centers across the world. Ray and the SunbeatablesTM is teaching more and more children the importance of sun safety. Our first Moon Shot-developed drug is in clinical testing. Our initial efforts are paying dividends thanks to you.

Second, as you read through the report, you will notice many names and projects are repeated across various Moon Shots and platforms. Drs. Elizabeth Shpall and Katy Rezvani. Ibrutinib. IACS-10759. Natural killer cells. Bloodbased biomarkers. We have denoted these collaborations (with an icon,

,)

to demonstrate the incredible cross-pollination of ideas that remains a hallmark of the Moon Shots Program. Created through the vision of former MD Anderson president Ronald A. DePinho, M.D., in 2012, the program’s focus on team science means that teams working within one disease site share ideas with their colleagues in another. Our platforms further emphasize this teamscience approach, as you will read that basic science discoveries often apply to many types of cancer. Such openness also demonstrates the massive benefit your philanthropy has for our patients. A gift to the Institute for Applied Cancer Science can benefit patients with leukemia as well as pancreatic cancer. A gift to the immunotherapy platform supports nearly all of the 13 disease sites and the more than 100 clinical trials to which the platform contributes. A gift to the proteomics platform supports the development of early detection and diagnostic blood tests for lung, pancreatic and prostate cancers.

All of this is possible because of you and your generosity. Your decision to support this unique effort is helping save lives and proving that progress against cancer doesn’t need to take decades. We can improve patient survival much faster through concentrated, team-oriented, well-supported science.

Our Moon Shots teams thank you. And our patients, three of whom you’ll read about in this report, thank you. You had the foresight to believe that advancements against cancer could be accelerated. You had the generosity to support MD Anderson’s comprehensive approach to team science. And you had the optimism to know that a world free from cancer is possible. Thank you.

TABLE OF CONTENTS Cancer Prevention and Control.............................................................................................. 4 HPV-Related Cancers Moon Shot.......................................................................................... 6 Melanoma Moon Shot.............................................................................................................. 7 Institute for Applied Cancer Science..................................................................................... 8 Center for Co-Clinical Trials..................................................................................................... 9 AML-MDS Moon Shot.............................................................................................................. 11 Adoptive Cell Therapy............................................................................................................. 12 CLL Moon Shot......................................................................................................................... 13 B-Cell Lymphoma Moon Shot............................................................................................... 15 High-Risk Multiple Myeloma Moon Shot............................................................................ 16 Breast Cancer Moon Shot..................................................................................................... 19 Ovarian Cancer Moon Shot...................................................................................................20 APOLLO......................................................................................................................................22 Cancer Genomics Laboratory............................................................................................... 24 Proteomics................................................................................................................................ 26 Lung Cancer Moon Shot........................................................................................................ 27 Pancreatic Cancer Moon Shot..............................................................................................29 Prostate Cancer Moon Shot.................................................................................................. 31 Colorectal Cancer Moon Shot...............................................................................................32 ORBIT..........................................................................................................................................33 Immunotherapy.......................................................................................................................34 Glioblastoma Moon Shot.......................................................................................................36

CANCER PREVENTION AND CONTROL

Estimates based on a broad range of scientific evidence indicate that more than 50% of cancers can be prevented. The cancer prevention and control platform aims to accelerate the development, dissemination and amplification of evidence-based strategies, community services, policy interventions

Program Leaders: Ernest Hawk, M.D., M.P.H.,

and knowledge-targeting measurable reductions in

Mark Moreno, Michael T. Walsh Jr.

cancer incidence and mortality at a population level.

Lung Cancer Moon Shot

access to screening and treatment as well as

EndTobacco is a platform initiative focused on

improving education and training for providers. This

preventing and reducing cancer through evidence-

year, the team initiated projects in the Caribbean and

based policies, prevention and cessation services. As a

expanded projects in Mozambique and South Texas.

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result of The University of Texas (UT) System Eliminate Tobacco Use initiative, all 14 system institutions are

Standard-of-Care Dissemination, BRCA

tobacco-free as of June 1, 2017. The initiative hosted

Through this project, the platform is improving

its second summit in April 2017 to share best practices

identification, genetic counseling and genetic testing

and discuss next steps as well as plan for expansion

uptake among a BRCA-mutation enriched population

efforts beyond the UT System. Cancer prevention

of patients with triple-negative breast cancer and

and control staff, working closely with MD Anderson’s

high-grade epithelial ovarian cancer and their close

Office of Governmental Relations, served as an

relatives at MD Anderson Physician Network locations.

educational resource to state and national partners on policy initiatives, such as Tobacco 21, a campaign

Project ECHO®

aimed at raising the minimum legal age for purchasing

Project ECHO (Extension for Community Healthcare

tobacco products to 21 years old. Additionally, the

Outcomes) is a capacity-building model that allows

EndTobacco program, in conjunction with

MD Anderson specialists to meet with and provide

MD Anderson’s Tobacco Treatment Program (TTP)

telementoring for advanced practice providers and

team, held over 70 tobacco cessation telementoring

physicians from rural and underserved areas in the

clinics for behavioral health professionals throughout

U.S, Latin America, Africa and other low-resource

Texas. With the continued collaboration with the TTP

settings. Primarily held through video conferencing,

staff, the cancer prevention and control platform team

sessions involve discussions of clinical guidelines and

successfully obtained a national accreditation that

best practices for management of select cancers,

trains health care professionals to become certified

cervical cancer prevention, tobacco treatment,

tobacco treatment specialists.

pathology, pharmacy operations and other related services, such as palliative care and survivorship.

HPV-Related Cancers Moon Shot

MD Anderson partnered with the ECHO Institute at

We are working to reduce the incidence and mortality

The University of New Mexico to become the first

of cervical cancer through targeted solutions and

oncology-focused Project ECHO Superhub in February

strategies in areas with a significant cervical cancer

2017, serving as a training and support site for other

burden in Texas, Latin America and sub-Saharan

organizations interested in developing Project ECHO

Africa. Through provider capacity building, affordable

programs with a focus on cancer. The first Project

technologies and health system strengthening, the

ECHO Superhub training took place in May 2017.

cancer prevention and control team is improving

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Melanoma Moon Shot: MD Anderson’s Office of Governmental Relations, the Melanoma Moon ShotTM and the cancer prevention and control platform served as clinical and scientific resources to state legislators, clinical colleagues and other key stakeholders on tanning bed prohibition legislation. A recent study, conducted by MD Anderson, found that 81% of indoor tanning facilities complied with Texas’ state law that bans tanning for minors, underscoring the importance of this approach as a strategy for skin cancer prevention. To date, 17 states and the District of Columbia now have tanning bed prohibition legislation. The platform team also worked closely with the CATCH Global Foundation to disseminate Ray and the Sunbeatables™ — a sun safety curriculum developed by MD Anderson for preschoolers, kindergarteners and first-graders — to new schools across the country. In June, the digital version of the program was launched at www.sunbeatables.org, which allows any user with an internet connection to access this curriculum for free. Next year, the platform plans to partner with a leader in comprehensive education solutions to reach even more children.

Be Well Communities™

Pasadena Vibrant Community

The mission of Be Well Communities is to mobilize

The mission of the Pasadena Vibrant Community

communities to promote wellness and stop cancer

is to mobilize Pasadena, Texas, to promote health

To reduce cancer incidence, we must put knowledge about cancer prevention and control into action in people’s daily lives.

before it starts. The

and wellness in the community. The initiative unites

inaugural community

individuals, schools, workplaces, government agencies,

is Baytown, Texas, the

health care providers and policy makers to carry

third-largest city in

out community-led solutions that will make positive,

Harris County. Over

long-lasting changes in people’s health. Through this

the past year, the team

collaboration, MD Anderson will be impacting close

established a community-based steering committee

to 33% of the Pasadena community through diet and

to develop a community action plan to deliver

physical activity interventions.

evidence-based interventions in partnership with key stakeholders. Through the community action

Thanks to your generous support, the cancer

plan, close to 66% of the Baytown community will be

prevention and control platform is positioned to help

impacted through education, programs and health

drastically reduce incidences of cancer around the

services.

world. Thank you.

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HPV-RELATED CANCERS MOON SHOT Program Leaders: Cathy Eng, M.D.; Lois Ramondetta, M.D.; Erich Sturgis, M.D., M.P.H.; Kathleen Schmeler, M.D.

Cathy Eng, M.D., professor of Gastrointestinal Medical Oncology Thanks to your generosity, the HPV-Related Cancers

We are making great strides in the laboratory, delving

Moon Shot™ is working to eliminate HPV-related

into the secrets of HPV cell lines and HPV-related

cancers in the future through prevention efforts

cancers. Cathy Eng, M.D., led a multi-institutional study

including vaccination and screening, while seeking

of the immunotherapy drug, nivolumab, for patients

more effective, less toxic treatments for patients

with anal cancer. In this study, nivolumab was used to

who are diagnosed with these cancers now. Your gift

catalyze the patients’ own T cells to fight metastatic

has allowed us to develop programs to increase HPV

anal cancer resistant to other therapies. Some cancer

vaccination rates in the United States and globally,

cells, such as advanced anal cancer, disrupt normal

to improve access to cervical cancer screening in

T cell immune function by binding to a receptor on

low-resource areas and to activate a first-of-its-kind

the T cells known as programmed death-1 (PD-1).

study to identify effective screening approaches for

This halts T cell function and prevents the T cells

noncervical HPV-related cancers. In addition, we

from killing the cancer cells. Nivolumab targets PD-1

are finding novel effective treatments for those with

and related proteins, releasing the T cells to kill more

HPV-related cancers, bringing discoveries from the

cancer cells. The study demonstrated an impressive

laboratory to the clinic across several disease sites.

response rate and was published in Lancet Oncology.

With your support, we are training health care

We are incredibly grateful for donors to the HPV-

professionals on proven methods to increase HPV

Related Cancers Moon Shot, who make our efforts to

vaccination rates in their clinics. Our approach

reduce the suffering caused by this disease possible.

distinguishes itself from other HPV vaccination education resources by combining provider education with quality improvement practices, such as setting up a standard process by which clinics remind patients to return for vaccination.

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Early results show improved HPV vaccination rates in key populations across Texas, and the program is expanding nationwide through the MD Anderson Cancer Network.

“These exciting results open a whole new field of opportunity to use the microbiome to potentially cure patients of cancer.”

— Jennifer Wargo, M.D.

MELANOMA MOON SHOT

Program Leaders: Jeffrey Gershenwald, M.D.; Michael Davies, M.D., Ph.D.; Jennifer Wargo, M.D.

With the development of more effective therapeutic

to immunotherapy, the first study of its type to look at

strategies, and thanks to the generosity of our donors,

this relationship. Using gut microbiome biospecimens

the Melanoma Moon Shot™ opened the first clinical

(stool) collected from patients, Dr. Wargo and her team

trial, led by Rodabe Amaria, M.D., and Melanoma

identified differences in the composition and diversity

Moon Shot co-leader Jennifer Wargo, M.D., evaluating

of the gut microbiome in patients that responded

neoadjuvant (presurgical) immunotherapies. Patients

to PD-1-directed therapy versus nonresponders.

are randomized to either a single agent presurgical

They learned that

regimen of nivolumab (standard of care for patients

those who responded

whose cancer cannot be removed by surgery or

better to anti-PD-1

that has metastasized) or a presurgical combination

immune checkpoint

therapy of nivolumab and the immunotherapy,

blockade therapy had

ipilimumab. In addition, our team is partnering with

a greater diversity

the immunotherapy and Cancer Genomics Laboratory

of bacteria types in

platforms to perform deep analyses of tissue acquired

their microbiomes,

from patients participating in these studies in the hopes

and those who responded better also had increased

of identifying mechanisms of response and resistance,

abundance of the Ruminococcaceae family of bacteria.

The potential to improve immunotherapy response by changing the composition of the gut microbiome is particularly exciting since it involves simple, nontoxic interventions such as altering one’s diet and taking probiotics.

further personalizing future treatment strategies.

None of these studies would be possible without the Another exciting project involves an examination

unwavering support of our donors. We are grateful for

of the role of the gut microbiome — the collective

your generosity.

population of microorganisms — in patient responses

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INSTITUTE FOR APPLIED CANCER SCIENCE Program Leader: Philip Jones, Ph.D.

The Institute for Applied Cancer Science (IACS)

Marina Konopleva, M.D., Ph.D., professor of Leukemia

was established in 2011 with the ambitious goal of Institute for Applied Cancer Science

advancing its first novel small molecule therapy into clinical testing within five years, and then producing a steady stream of subsequent clinical candidates that move into clinical trials. Now, in 2017, the IACS platform, in close collaboration with the translational biology capabilities of the Center for Co-Clinical Trials (CCCT)

IACS-10759

Center for Co-Clinical Trials

platform, is delivering on its promise thanks to the support of our generous donors. We have produced an exciting project portfolio with multiple agents expected

AML-MDS Moon Shot

to enter clinical testing in 2018. This momentum underscores the mission of IACS — to bring impactful therapies to cancer patients through bench-to-bedside drug development.

Pancreatic Cancer Moon Shot More clinical studies are opening to enroll melanoma,

Our most advanced project, IACS-10759, entered clinical

pancreatic and breast cancer patients because a

trials this year for safety and efficacy studies in patients

metabolic starvation approach can be applied to other

with relapsed/refractory acute myeloid leukemia (AML).

malignancies.

IACS-10759 is a novel drug targeting cancer cells’

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mitochondria, the tiny cellular organelles that

Several programs are following closely on the heels of

produce metabolic energy. Cancer cells require a lot

IACS-10759. Over the past year, a wealth of preclinical

of energy to constantly replicate and grow, and several

data has been generated through cooperation

types of cancers depend on mitochondria for energy.

among IACS, CCCT and MD Anderson clinicians to

Targeting mitochondria in these cancers is essentially

support clinical trials for a second IACS-developed

draining the cancer cells’ batteries to starve them.

small molecule. This drug candidate, IACS-06274,

The clinical trial, led by Marina Konopleva, M.D., Ph.D.,

inhibits glutaminase, another enzyme critical for

professor of Leukemia, and Naval Daver, M.D., associate

energy production and the supply of cellular building

professor of Leukemia, is the result of a partnership with

blocks. Like IACS-10759, this drug also drains cancer

the AML-MDS Moon Shot™ and a $3.5 million grant from

cells of an essential energy source, but it targets a

the Leukemia and Lymphoma Society. The drug has

metabolic process rather than mitochondria. The drug

shown to be well tolerated in the patients treated to date,

is undergoing toxicology studies and clinical supplies

effectively shutting down the mitochondria in AML cells.

manufacturing in accordance with FDA regulations for

first-in-human clinical evaluations. Rigorous preclinical

Since February 2017, this collaboration has driven two immuno-oncology projects toward the clinic, and both have potential to be tested in patients in 2018.

testing is demonstrating how this potential drug can modulate the immune system to further affect the cancer cell’s biology. It is on track to enter clinical evaluation in summer 2018 in studies with the Lung Cancer Moon Shot

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Another project targets a protein frequently mutated

and Ovarian Cancer Moon Shot .

TM

in both hematological malignancies and solid tumors that also acts as a resistance mechanism in a number of

Strategic partnerships with pharmaceutical companies

commonly used targeted therapies. The IACS and CCCT

will be essential in bringing our drugs to more cancer

teams have discovered an innovative approach to shut

patients. The IACS team has advanced two projects with

down signaling by this oncogene and are advancing

TESARO Inc., an oncology-focused biopharmaceutical

novel therapies into late-stage preclinical testing and,

company.

hopefully, in clinical trials in 2018.

CENTER FOR CO-CLINICAL TRIALS

The CCCT collaborates with Moon Shots teams and the Institute for Applied Cancer Science (IACS) — MD Anderson’s small molecule drug discovery platform — to evaluate novel therapeutics in sophisticated preclinical models. In addition to safety and efficacy studies, the CCCT performs biological

Program Leaders: Joseph Marszalek, Ph.D.;

studies to determine which patients may benefit from

Tim Heffernan, Ph.D.

therapy and develops mechanisms to identify these patients.

Despite recent notable successes in

In 2016, our collaborative work with IACS yielded the

oncology drug development, only 5% of

first entry of a novel therapeutic from MD Anderson

experimental cancer drugs prove effective

into a clinical study. The CCCT collaborated with

when tested in clinical trials. One factor

investigators from eight Moon Shots to accelerate

contributing to this high failure rate is the

the translation of IACS-10759, an inhibitor of cancer

advancement of drugs into clinical testing

energetics, and defined patient subpopulations

without sufficient biological insight to

for clinical evaluation. Through extensive preclinical

guide patient selection. This is a costly

testing, the CCCT and our clinical collaborators designed

and inefficient approach that exposes

this first-in-human study in patients with acute myeloid

an overwhelming majority of patients to

leukemia, and we initiated an additional Phase I study in

futile therapies. To address this problem,

patients with pancreatic and breast cancers, as well as

MD Anderson established the Center for

melanoma in the third quarter of 2017.

Co-Clinical Trials (CCCT), a Moon Shots

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platform with an unprecedented focus on

Our preclinical activities also have supported the

translational biology. The goal of the center

development of the broader IACS drug discovery

is to provide the world-class faculty of

portfolio, which is poised to advance five novel

MD Anderson the necessary insights to

therapeutic modalities into the clinic by the end

deliver transformative medicines to our

of 2018. This includes IACS-06274, an inhibitor of

patients.

glutaminase, which is a critical metabolic enzyme

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that fuels tumor growth. Through a comprehensive

that may enhance the activity of BTK inhibitors. In

translational effort, we have identified biomarkers

collaboration with the Melanoma Moon ShotTM and

designed to predict sensitivity to IACS-06274 in

Lung Cancer Moon ShotTM, we have initiated preclinical

patients diagnosed with non-small cell lung cancer

trials to analyze how targeted therapies may be

or high-grade serous ovarian cancer. The CCCT is

used to enhance the activity of immunotherapies.

currently executing FDA-mandated studies to support

In addition, the CCCT has completed a series of

the filing of an Investigational New Drug application for

preclinical studies with the Breast Cancer Moon ShotTM

permission to initiate Phase I clinical studies in 2018.

to identify targeted therapies that would enhance the activity of PARP inhibitors in triple-negative breast

In addition to evaluating novel therapeutics, the CCCT collaborates with Moon Shots to test hypotheses that may reposition or enhance the impact of cancer drugs.

cancer. With your generous support, these efforts have helped prioritize new effective therapeutic combinations that are progressing toward clinical trials conducted by Moon Shots leadership.

Recent efforts include a partnership with the CLL Moon ShotTM team to evaluate drug combinations

Jeffrey Kovacs, Ph.D., institute senior research scientist in the CCCT

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AML-MDS MOON SHOT Program Leaders: Guillermo Garcia-Manero, M.D.; Hagop Kantarjian, M.D.

The Moon Shots ProgramTM has developed multiple translational research initiatives significantly impacting

Investigators led by Richard Champlin, M.D.,

our understanding of myelodysplastic syndromes

have developed new stem cell transplant

(MDS) and acute myeloid leukemia (AML). Our effort

technologies using and targeting natural killer

is collaborative, bringing together investigators in

(NK) cells to improve transplant outcomes.

Leukemia and Stem Cell Transplantation along with

Examples include the use of ex vivo expanded

those from several platforms. And your generous

NK cells (cells that have been multiplied in

support has made this progress possible.

the lab before infusion) that are now being tested in Phase II clinical trials to enhance

One of the most significant discoveries in the

the graft-versus-leukemia effect of stem cell

biological sciences over the past two years has

transplantation. In addition, investigators

been the identification of mutations in the blood of

are working on boosting the efficacy of NK

some patients without disease. This phenomenon

cells by targeting a specific leukemia antigen

is known as clonal hematopoiesis or CHIP. Initial

known as PR1.

data indicated that CHIP is associated with an increased risk of developing leukemia. Investigators at MD Anderson, with the support of the Cancer

related leukemia in patients with CHIP.

Genomics Laboratory, have taken this observation forward by demonstrating that nearly 75% of patients

A significant collaboration between our team and IACS

with therapy-related leukemia have evidence of CHIP.

resulted in the development of the agent IACS-10759.

Knowing that CHIP can help identify patients at risk for therapy-related leukemia is transformative, as it allows us to develop preventive strategies.

This concept — unimaginable just a couple of years ago — is already being applied to our patients at MD Anderson.

Therapy-related

IACS and the AML-MDS Moon ShotTM team designed,

leukemia is very

synthesized and tested more than 800 compounds

aggressive with a

through this process to arrive at IACS-10759. In a

poor prognosis and

Phase I clinical trial, seven patients already have

occurs in patients

been treated without significant toxicity.

who were treated with chemotherapy

Finally, a new project initiated in the last year, led

or radiation for

by Michael Andreeff, MD., Ph.D., focuses on the

lymphoma, myeloma

eradication of residual leukemic stem cells in patients

or solid tumors. In collaboration with the High-Risk

in remission after successful chemotherapy. This

Multiple Myeloma Moon ShotTM and B-Cell Lymphoma

program already has proven that it is possible to

Moon Shot™, we are studying the incidence of CHIP in

isolate these residual cells in patients, leading the way

patients receiving autologous stem cell transplantation

to newer curative strategies for patients with AML.

(in which patients’ own cells are treated and infused back into them). This group is at highest risk of

We are very proud of this effort, achieved only with

developing therapy-related leukemia. In parallel,

your support. We believe that this Moon Shot is

investigators led by Guillermo Garcia-Manero, M.D.,

significantly contributing to the continuous cure of

are designing clinical trials with low doses of epigenetic

patients with AML and MDS.

therapy and immunotherapy to prevent therapy11

ADOPTIVE CELL THERAPY Program Leaders: Elizabeth Shpall, M.D., Cassian Yee, M.D.

The adoptive cell therapy platform programs immune

preclinical evidence that demonstrates the death of

cells to recognize and attack cancer. We are excited

leukemia cells upon infusion. Your support has made

about a number of projects, including the development

this exciting work possible.

of novel cord blood-derived natural killer (NK) cells for patients enrolled in trials from the AML-MDS Moon

In collaboration with the CLL Moon Shot, we have

Shot , High-Risk Multiple Myeloma Moon Shot

designed cord blood NK cells carrying the CAR

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With technology developed right here at MD Anderson, we have multiplied NK cells in the lab and — for the first time ever — infused them back into patients, providing a far larger dose of tumor-killing NK cells.

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and

Chronic Lymphocytic

targeting the CD19 protein, a strategy designed to

Leukemia (CLL) Moon

make the NK cells even more potent and effective

ShotTM. Chimeric

at eliminating CD19-positive cancers. Additionally,

antigen receptor

the platform is producing two adoptive cell therapy

(CAR) T cell therapy

products for the Melanoma Moon Shot™: tumor-

involves engineering

infiltrating lymphocytes (TILs) and endogenous T cells

T cells to recognize

(ETC). Patients with metastatic melanoma will receive

specific antigens

intravenous TILs in conjunction with the check-point

the cancer cells express. We then expand them and

inhibitor, pembrolizumab, while personalized ETC will be

infuse them back into the patient. While effective, this

used to treat uveal melanoma with liver metastases.

approach has drawbacks, including the fact that the T cells have to come from the patient to avoid the risk

Another exciting project in the validation phase will use

of graft-versus-host disease. NK cells from a normal

allogeneic (taken from a donor) bone marrow-derived

umbilical cord blood donor, however, can be engineered

mesenchymal stem cells loaded with the tumor-

to express CARs, expanded and then stored for use

selective oncolytic adenovirus, DNX-2401, for patients

in virtually any patient. This off-the-shelf approach

with recurrent glioblastoma, a disease for which few

eliminates not only the need for creating a new batch

therapeutic options exist.

of tumor-targeting cells for each patient, but also the

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weeks-long wait that goes with doing so. The cells even

None of the work we are able to do to support the

include a “suicide gene” that allows us to eliminate them

Moon Shots ProgramTM would be possible without your

if they are found to cause substantial toxicity. We have

support. Thank you.

Adoptive Cell Therapy

CARmodified NK cells

CLL Moon Shot

B-Cell Lymphoma Moon Shot AML-MDS Moon Shot

Left: Katy Rezvani, M.D., Ph.D., and Elizabeth Shpall, M.D.

CLL MOON SHOT Program Leaders: Michael Keating, M.B., B.S.; William Plunkett, Ph.D.; William Wierda, M.D., Ph.D. We are excited to share the advances made during the

Ibrutinib has now been adopted as frontline therapy

past year in the Chronic Lymphocytic Leukemia (CLL)

for most CLL patients. Yet there remain curative

Moon Shot . In last year’s report, we detailed our

limitations to this breakthrough drug, and prolonged

involvement in the breakthrough therapies venetoclax

use of it can be expensive, costing more than

and ibrutinib. Thanks to your continued support,

$130,000 per year. For many patients it is not feasible

we were able to build upon our discoveries and

— physically or financially — to continue on this

experiences to push the envelope further.

therapy. To better serve CLL patients, Varsha Gandhi,

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Ph.D., professor of Experimental Therapeutics, Immunotherapy has been a hallmark of our program

conducted studies to determine whether lowering

since inception, and all the hard work is beginning

the dose of ibrutinib would be safe for patients while

to pay off. Katy Rezvani, M.D., Ph.D., professor of

still being effective. Based on her initial investigations

Stem Cell Transplantation and Cellular Therapy,

in the laboratory and a pilot clinical trial, we believe

helped to develop a novel therapy that uses NK

that a lower dose of ibrutinib is optimal and can

cells modified by CARs to target and kill CLL cells.

achieve the necessary therapeutic effect for patients.

The CAR NK cell program has reached clinical trial

We will be launching a Phase II study to confirm these

status and we are beginning to enroll patients in a

findings. Ultimately, lower doses of ibrutinib will mean

first-in-human study. We are sincerely grateful that

less toxicity and lower costs — a win-win for patients

your generosity has led us to this significant milestone,

and providers!

which has filled us with hope for a potential curative therapy for our patients.

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Our team is also devising another strategy to

just three months, the patient is showing a complete

overcome ibrutinib’s limitations. One of the

response on his PET imaging and continues on the

immunotherapy studies we initiated last year

clinical trial.

combined ibrutinib with nivolumab. Although it appeared at first to have minimal effect on the disease, we discovered that this unique combination significantly benefits patients with Richter’s Transformation — a syndrome in which

This kind of response for Richter’s Transformation patients was nearly unheard of before this study — and there are many more stories like this.

CLL transforms to a highly aggressive form of B-cell lymphoma associated with poor prognosis. One of

This is an exciting time for the CLL Moon Shot as we

the patients on the trial had already been treated

see years of effort come to fruition for the benefit

with chemotherapy and ibrutinib for more than two

of our patients. Thanks to you, and other generous

years before developing Richter’s Transformation. His

donors like you, we are moving closer to eradicating

oncologist recommended our clinical trial combining

CLL once and for all.

ibrutinib and nivolumab, led by Nitin Jain, M.D. After

Betty Lamothe, Ph.D., assistant professor of Experimental Therapeutics, in the lab

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B-CELL LYMPHOMA MOON SHOT Program Leaders: Richard Champlin, M.D.; Michael Wang, M.D.

With support from our donors, the B-Cell Lymphoma

Transplantation and Cellular Therapy, and fellow Moon

Moon Shot

Shot team members have addressed this problem

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team has continued to address problems

that stand in the way of better outcomes for our

with CAR T cells that are primed to recognize and kill

patients.

lymphoma. A multicenter clinical trial of CAR-modified T cells in relapsed B-cell lymphoma (mostly DLBCL),

One of the biggest problems we face is how to prevent

led by Sattva Neelapu, M.D., associate professor of

lymphoma from returning after initial therapy, at which

Lymphoma/Myeloma, produced stable complete

point it often shows resistance to further treatments.

remissions in about 40% of patients, many of whom

Up-front intensive therapy — which is harsh but

had run out of treatment options. Based on these

effective — offers the best chance for mantle cell

trial results, the FDA approved this type of CAR T cell

lymphoma (MCL) cure.

therapy in October of 2017, and combination trials using CAR T cells are underway or planned.

Working with the Cancer Genomics Laboratory, we successfully identified a predictor of how patients respond to treatment based on the genetic make-up of their tumors.

One limitation of CAR T cells is that they are not yet available for all patients who need them, partly because they are made from the patient’s own T cells

This will allow us to stay one step ahead of the

in a somewhat time-consuming process. In contrast,

disease and turn immediately to more effective

natural killer (NK) cells do not need to be patient-

options if one therapy begins to fail. Michael Wang,

specific and are available “off-the-shelf” from banked

M.D., professor of Lymphoma/Myeloma, designed

umbilical cord blood. Katy Rezvani, M.D., Ph.D., and

a trial to add the targeted agent ibrutinib, which

Elizabeth Shpall, M.D., have shown that unmodified

inhibits specific features of lymphoma cells, to

NK cells have natural antitumor effects and are safe to

combination chemotherapy. Using a “window” trial

give to patients. They also have confirmed in mouse

design that administers ibrutinib (and rituximab) prior

models that CAR-modified NK cells derived from cord

to chemotherapy, Dr. Wang’s team achieved a 100%

blood are longer lasting and have stronger cancer-

rate of complete remission in previously untreated

killing ability. In collaboration with the adoptive

MCL patients. This result alone, if confirmed in

cell therapy platform, we have recently launched

larger studies, will increase the efficacy of frontline

MD Anderson’s first-in-human clinical trial of

MCL treatment while reducing its toxicity and could

cord blood-derived CAR NK cells for lymphoma.

potentially provide the basis for future testing of

Additionally, Jeffrey Molldrem, M.D., is identifying new

combinations that are entirely chemotherapy-free.

antigen targets for effective immunotherapy using monoclonal antibodies or antigen-specific T cells.

We also seek to improve outcomes for the nearly 10,000 new patients each year in the U.S. who relapse

Our team deeply appreciates our donors’ generosity,

after initial therapy for diffuse large B-cell lymphoma

which has made our research efforts and achievements

(DLBCL), a common but aggressive form of the disease.

possible and will profoundly impact the lives of those

Current options are highly toxic and less than 25%

saved. Working together, we will reach the ultimate goal

curative. Richard Champlin, M.D., chair of Stem Cell

of doubling the cure rate of B-cell lymphoma.

15

HIGH-RISK MULTIPLE MYELOMA MOON SHOT Program Leaders: Robert Orlowski, M.D., Ph.D.; Eric Davis, M.D.; Donald Berry, Ph.D.

Multiple myeloma (MM) is the second most commonly

in remission; this is the first report of any response

diagnosed hematologic malignancy, with the rate of

to a single-agent immunotherapy in smoldering MM.

new cases expected to grow by almost 60% from

Even more encouraging, myeloma cells from this

2010 to 2030, due in part to our aging population.

particular patient harbored one of the most serious

While current therapies for multiple myeloma are not

genetic abnormalities, del17p, which is associated with

curative, they can extend survival for many years,

poor prognosis. Overall survival of patients with this

meaning virtually all patients will develop and succumb

abnormality after progressing to symptomatic MM is

to relapsed/refractory multiple myeloma.

only two to three years. All but one of the remaining patients on this trial have stable disease.

In view of the difficulty and growing size of the problem posed by multiple myeloma, the High-

In the second trial, we are targeting a specific

Risk Multiple Myeloma Moon Shot™ is pursuing a

molecule, CD38, on the surface of myeloma cells with

bold solution: to cure the disease before it evolves

an antibody called isatuximab, intended to elicit an

into the symptomatic stage. Multiple myeloma has

anti-myeloma immune response. This trial opened in

well-defined, easily detectable precursor states

February 2017, and the first patient showed a partial

— monoclonal gammopathy of undetermined

response after just one round of therapy.

significance, and smoldering multiple myeloma — both of which carry a lifetime risk of progression to

In collaboration with Moon ShotsTM platforms,

symptomatic MM. However, even high-risk patients

characterizations of myeloma and immune cells from

are currently not treated, largely because toxicities

patients on these trials will help us understand the

associated with available chemotherapies outweigh

differences in their responses, and ultimately will

any benefit.

help us in the design and patient selection of future clinical trials.

But we now have new, less toxic immunotherapies that have given us an opportunity to intervene with

These early results convince us that we are on the

patients early to improve their long-term outcomes.

right track. With your support, we are moving toward

Our Moon ShotTM has opened two clinical trials to show

launching larger trials of immunotherapy in precursor

that novel immunotherapies can delay or prevent

states of MM, improving our analysis of samples and

intermediate- and high-risk patients from developing

better understanding how the immune system can

symptomatic MM.

prevent progression to symptomatic disease.

Progression from smoldering MM to symptomatic MM may be caused by exhaustion and/or inhibition of the patient’s immune system by myeloma cells.

One of our trials uses pembrolizumab, an antibody designed to wake up or restore the patient’s immune system. One patient achieved a complete response after just three rounds of pembrolizumab and remains

16

”The very best way to help our patients is to cure myeloma before it ever evolves into the symptomatic phase. These trials show the promise of doing just that.”

— Robert Orlowski, M.D., Ph.D.

“I'm not as afraid of a possible relapse as I once was, largely due to new drug therapies for relapsed and refractory disease.”

— Karen Fore, multiple myeloma survivor

My Multiple Myeloma Moon Shot

by Karen Fore

In June 2010, I was diagnosed with multiple

I'm not as afraid of a possible relapse as I once

myeloma, a blood cancer that attacks the bone

was, largely due to new drug therapies for relapsed

marrow, bones and kidneys. I'd never heard of

and refractory disease. Knowledge is power;

it, even though I'd worked in the medical field

therefore, I set out to keep up with the most current

for decades. I began chemotherapy almost

developments for multiple myeloma treatment. The

immediately, with little results. We tried a second

progress is extremely exciting!

line of treatment and it also failed. Eventually, I was enrolled in a clinical trial that controlled the

I was thrilled that multiple myeloma was chosen

disease enough to proceed to a stem cell transplant.

to be part of the Moon Shots Program™. They're

Thankfully, 18 months later, I achieved a complete

researching how the body can use its own immune

response and have been blessed to maintain this

system and special killer cells to eradicate the

remission to this day.

myeloma cells from the body — in other words, a cure! There's hope for those diagnosed with multiple

This is a disease that currently has no cure, however,

myeloma. With the intensive research being done

and can recur at any time. I hold my breath with

through the Moon Shots Program, I believe this cure

each follow-up visit hoping that I'm still in remission.

will come in my lifetime.

This story originally appeared on Cancerwise, MD Anderson’s blog for patients, caregivers and survivors: www.cancerwise.org.

17

Breast cancer cells (above) are the result of mutations in the tumorsuppressing gene, BRCA, in 5 to 10% of all breast cancer patients. Moon Shot investigators are using targeted therapies to attack BRCA-associated tumors.

18

BREAST CANCER MOON SHOT

Program Leaders: Junjie Chen, Ph.D.; Stacy Moulder, M.D.

Precision medicine is the use of modern

Jennifer Litton, M.D., and Banu Arun, M.D., lead the

molecular testing and/or imaging to identify and

Breast Cancer Moon Shot’s Uncommon and Rare

target abnormalities in cancer cells that possess

Breast Cancer Initiative, currently testing targeted

characteristics that make them vulnerable to

therapies in select patient populations. Their exciting

therapeutic attack. Recently, we have improved breast

work has resulted in complete disappearances of

cancer cure rates due, in part, to our ability to identify

cancer within the breast and surrounding lymph

and treat newly diagnosed patients at high risk of

nodes in patients with BRCA-associated tumors

having small, undetectable deposits of cancer cells

treated with targeted therapy before surgery.

in their bodies that will develop into tumors if left untreated. A goal of the newly formed Breast Cancer

When chemotherapy alone or combined with targeted

Moon Shot

therapies causes a complete response in the breast,

TM

is to use precision medicine to cure

breast cancer.

the prognosis is exceptionally good because the drug also is likely killing tumor cells elsewhere in the body

The innovative ARTEMIS trial studies triple-negative

that are too small to detect.

breast cancer, an especially aggressive form of breast cancer, for which no common targeted therapy exists. In less than two years, this trial has molecularly profiled nearly 200 individual triplenegative cancers, generating information that will best allow us to predict response based on specific genetic profiles. Approximately 30 of these tumors have been identified as unresponsive to chemotherapy,

“The early finding that a single targeted drug can cause a complete, durable response if used in the right patient population is especially promising and suggests that one day, patients can avoid chemotherapy altogether.”

— Jennifer Litton, M.D.

indicating a 40 to 80% risk of death within three years

The Breast Cancer Moon Shot also supports unique

of diagnosis. We have enrolled nearly all of these

hypothesis-driven research into the causes of drug

patients with tumors unresponsive to chemotherapy

resistance, which helps us to develop promising new

into clinical trials with targeted therapies selected

treatment strategies. Helen Piwnica-Worms, Ph.D., uses

based upon the molecular profiling of their tumor.

tumor tissue from clinical trials in triple-negative breast

The results to date have been promising. We also are

cancer and BRCA-associated cancers and implants

testing exciting new imaging techniques to identify

them into mice to create patient-derived xenograft

cancers that are resistant to chemotherapy because

(PDX) models. Researchers then perform molecular

of poor blood supply or the presence of “drug pumps”

characterizations on both patient samples and PDXs

within cancer cells that remove chemotherapy before

pre- and post-therapy; the differences we discover

it has a chance to work.

help us to determine causes of resistance, leading to promising new treatment strategies that we can test in

An important component of breast cancer is its

PDXs prior to entering clinical trials in patients.

nature as a diverse disease that can be grouped into numerous subtypes, each of which requires a different

Your support has a multiplier effect, as it has provided

targeted therapy to cure patients. Because of our

infrastructure and preliminary data for successful

substantial patient volume and faculty expertise, we

grant applications that have procured over

are optimally positioned to develop targeted therapy

$13 million in funding for the institution.

strategies in this age of precision medicine.

Thank you for making our work possible.

19

OVARIAN CANCER MOON SHOT Program Leaders: Anil Sood, M.D.; Gordon Mills, M.D., Ph.D.; Shannon Westin, M.D.

In 2010, Diane Sarver was diagnosed with stage IV

to chemotherapy altogether. Over the past few years,

ovarian cancer. One round of chemotherapy put

with the support of our committed donors, the Ovarian

Diane into remission, but two-and-a-half years later

Cancer Moon Shot team has launched several clinical

she would have her first ovarian cancer recurrence;

trials to address recurrent, therapy-resistant tumors.

she would go on to have two more recurrences. Diane

The team asks: Can we use a personalized approach to

knew it was time to seek other options and came to

chemotherapy for our patients with recurrent disease

MD Anderson. She enrolled in a clinical trial aimed at

in an effort to increase durable remission?

treating recurrent disease through the Ovarian Cancer Moon Shot™. This year marks Diane’s third year on the

The program has developed a portfolio of clinical trials

trial and second year in remission.

to better understand the DNA of ovarian cancer cells.

Currently, the Ovarian Cancer Moon Shot includes

20

One of the Ovarian Cancer Moon Shot’s first

more than 15 clinical trials. With generous donor

accomplishments was the development of the

support, we have taken exciting benchmark data

Anderson Algorithm, a personalized surgical approach

and translated the findings into the clinic. One of the

to cancer therapy. This protocol substantially increases

goals is to understand the mechanisms that help a

the frequency of complete visible tumor removal,

cancer cell repair its damaged DNA when treated with

which has been shown to increase patient survival,

chemotherapy. If we determine what helps the cancer

in women undergoing upfront debulking surgery.

cell thrive, we can target that element of resistance

While the algorithm is a groundbreaking approach

to destroy the cancer cell permanently. As part of

to frontline therapy, ovarian cancer is a disease that

our ongoing trials, we obtain pre- and post-treatment

frequently returns and eventually becomes resistant

biopsies to elucidate resistance mechanisms.

Diane Sarver, ovarian cancer survivor

Our work has shed light on an enzyme known as

Even further, as a companion to our PARP and related

PARP, which helps cancer cells by repairing DNA when

clinical trials, we have implemented patient-reported

it is damaged by chemotherapy. Our work also has

outcomes measurement tools to identify patients who

explored how to “re-sensitize” tumors that evolve to

may be at risk for side effects and less positive clinical

By focusing on making an already available drug more effective, we hope to increase the number of therapeutic options available for our patients.

resist PARP inhibitors,

outcomes.

and we have developed clinical trials for patients

MD Anderson’s Moon Shots Program™ demonstrates

who recur after PARP

our commitment to innovative research toward

inhibitor treatment.

eradicating cancer. This would not be possible without the generous support of our donors, and we take

Diane is a clinical trial patient on one of our PARP

this opportunity to graciously thank you for your

inhibitors. Thankfully, her story of survivorship is not

partnership in Making Cancer History ®.

unique. Implemented in 2014, the trial has enrolled 42 ovarian cancer patients. Preliminary analysis of the data demonstrates the drug combination is well tolerated and shows activity against tumor cell growth.

We are pleased to report other clinical trials in our portfolio are proving to be just as effective in the fight to prevent ovarian cancer recurrence.

“A clinical trial can be life-changing and life-sustaining. Gain knowledge, ask questions and learn to become your own best advocate.”

— Diane Sarver, CancerWise, April 2017

21

APOLLO Program Leaders: Andrew Futreal, Ph.D.; Ignacio Wistuba, M.D.

The Adaptive Patient-Oriented Longitudinal Learning and Optimization (APOLLO) platform of MD Anderson’s Moon Shots Program™ is aimed at the standardized collection of highquality research specimens before, during and after a patient’s treatment. By providing critical phenotype data paired with patient clinical data across cancer types, APOLLO accelerates discoveries and practice-changing patient outcomes. Moon Shot™ teams and other interested collaborators have successfully collected longitudinal patient samples thanks to a universal banking consent form that allows APOLLO to study high-interest patient clinical trials.

APOLLO is designed to make advanced cancers more predictable and easier to defeat by focusing on the malignancy’s relentless ability to evolve and survive in response to treatment. APOLLO is powered by the expert sequencing capabilities and comprehensive molecular analyses of the Cancer Genomics Laboratory. The platform offers a paradigm-changing approach that accelerates the development of new methods based on scientific discoveries.

Thanks to generous donor support, in October 2016, APOLLO expanded the list of projects for which it is collecting biospecimens beyond the original pilot projects. A novel immunotherapy clinical trial for stage IV metastatic melanoma patients, for example, demonstrates how APOLLO is enabling the kind of comprehensive analysis of patient samples that is becoming the gold standard of cancer care.

Nancy Pinkston, melanoma

22

survivor, benefits from APOLLO's

The trial involves pre- and post-surgical

comprehensive surveillance approach.

treatment with a form of immunotherapy —

pioneered by immunotherapy platform leader, James

drug predicted which patients would respond. Pre-

Allison, Ph.D. — called immune checkpoint blockade,

treatment biopsies, however, didn’t find predictive

which frees the immune system to attack cancer,

genomic or immune biomarkers.

rather than attack cancer directly.

Andrew Futreal, Ph.D., co-leader of APOLLO and the Nancy Pinkston joined the trial after a relapse

Moon Shots ProgramTM, knows that finding predictive

of her melanoma. She received four rounds of

biomarkers in pre-treatment biopsies is the Holy Grail,

immunotherapy (nivoumab) and then underwent

but he believes that pre-treatment and early on-

surgery in May 2017. Following surgery, Nancy got the

treatment biopsies might be a winning combination.

good news from Jennifer Wargo, M.D., co-leader of the Melanoma Moon Shot and associate professor

“We don’t take one CT scan initially and then use

of Genomic Medicine and Surgical Oncology: “All she

that same scan to assess how well treatment is

found at surgery was dead tissue and the biopsy

working three months later,” notes Dr. Futreal. “We

confirmed the good news — no evidence of disease.”

take a new scan.”

Clinical trial participants like Nancy are helping

A cancer patient generally undergoes a biopsy before

Dr. Wargo and her colleagues address a vital question:

starting treatment. After that, standard practice is to

Why do immunotherapy drugs work well for some

track the tumor’s progression using CT or MRI scans

patients, like Nancy, and briefly or not at all for others?

for size and volume and PET scans for metabolic activity. The APOLLO platform seeks to improve upon

Nancy agreed to repeat biopsies during her melanoma

this standard practice.

treatment, beyond the usual pre-treatment biopsy.

Dr. Wargo is a leader of an effort to employ deep molecular and immune analysis of tumors before, during and after treatment to understand who benefits, who doesn’t and what to do next after any treatment fails.

“If you don’t get a biopsy before, during and after treatment, you aren’t going to learn about how tumors evolve and resist treatment.”

— Ignacio Wistuba, M.D. Nancy Pinkston completed her immunotherapy in

“We should be incorporating this sort of biopsy and

late 2016 with no side effects from treatment. Her

blood sample analysis into clinical trials, and ultimately

experience demonstrates how the APOLLO platform is

we may even incorporate this into treatment with

leveraging a relatively new understanding of cancer —

standard-of-care therapy. This effort is critical to

that it can behave differently before, during and after

guiding patient care in this era of precision medicine,”

treatment — to find the best course of treatment for

Dr. Wargo says.

our patients. Such a comprehensive effort would not be possible without the generous support of donors.

In the next two years, APOLLO is scheduled to conduct such analyses in 2,100 patients enrolled in 28 high-

APOLLO

priority clinical trials for melanoma; multiple myeloma; glioblastoma; lymphoma; lung, breast, colorectal, pancreas and ovarian cancers; sarcoma; and cancers caused by the human papillomavirus.

A solid tumor pilot study using the APOLLO approach

Genomic sequencing

Cancer Genomics Laboratory

led by Dr. Wargo found that analyzing biopsies taken early during treatment with a similar immunotherapy

23

CANCER GENOMICS LABORATORY Program Leaders: Andrew Futreal, Ph.D.; Kenna Shaw, Ph.D.

Next-generation sequencing has transformed how

that ensures data from multiple platforms are consistent

cancer is diagnosed and treated. Scientists now can

and comparable.

identify changes to the genes that control cell function, particularly genes that regulate how cells grow and

Thanks to recent technology developments, we have

divide. Because every person’s cancer is different and

implemented protocols to increase efficiency and allow

every tumor has its own unique abnormalities at the

for reliable sequencing of low-quantity and low-quality

genetic level, MD Anderson clinical researchers can

DNA/RNA samples. We are developing a targeted

Researchers analyze the gene sequence in the tumor and compare it to the same individual’s normal gene sequence. The differences identify where potential targets may lie.

determine whether a

gene panel to interrogate cell-free DNA (cfDNA) —

patient’s tumor carries

bits of DNA floating free in the bloodstream that may

clinically significant

be signposts of disease. Cell-free DNA obtained by a

mutations that make

simple blood draw would reduce the need for invasive

it vulnerable to a

and expensive biopsies. In addition, we have deployed

particular drug or

two new targeted gene sequencing panels that focus

therapy.

on specific genes or gene regions that have a known or suspected association with the cancer of interest. For

The Cancer Genomics Laboratory platform of

example, the solid tumor panel was updated to include

MD Anderson’s Moon Shots ProgramTM performs

DNA damage response genes and was co-developed

next-generation sequencing for all of the Moon Shots

with input from five Moon Shots.

and provides molecular analyses of genomic DNA and transcriptomic RNA, which has a significant impact on

Finally, we are in the last steps of implementing an

the detection, management and treatment of cancer.

immuno-oncology gene expression assay. Immunooncology seeks to answer questions about why the

Over the past year, and with your generous support,

immune system does not recognize and destroy

we have sequenced more than 3,000 samples

cancer cells. The assay, which requires minimal sample

from 11 diseases. Nearly 50% of our sequencing

input, would identify certain molecular markers that

efforts were directed at leukemia samples for the

may enable the immune system to recognize and

APOLLO platform, which tracks the mutational

stamp out tumor cells. Applications such as these

changes of cancers at strategic points throughout

are designed to address specific biological and

treatment so that we can better understand the

clinical questions that are necessary to further our

behavior of cancer cells.

understanding of cancer and propel new discoveries.

These milestones could not have been reached

The resulting high-quality data then flows into the Big Data Enterprise Warehouse designed to store and allow access to that information for all MD Anderson researchers. This means cancer experts can use data created for one type of cancer that might have an impact on another type of cancer. The Cancer Genomics Laboratory serves as an essential part of the pipeline

24

without your support.

Lin-Ya Tang, coordinator, in the Cancer Genomics Laboratory

25

PROTEOMICS Program Leader: Sam Hanash, M.D., Ph.D.

The proteomics platform helps investigators identify proteins or molecules in the blood that are useful for the detection and diagnosis of cancer. The platform also helps identify new targets for cancer treatments.

Lung cancer remains the top cause of cancer deaths worldwide. While smoking is the primary culprit of the disease, this statistic includes an increasing number of never-smokers as well as those who do not meet the current risk criteria to trigger CT screening for

Sam Hanash, M.D., Ph.D. Colorectal Cancer Moon Shot

lung cancer. Based on a critical need for a simpler diagnostic method, we have made significant progress in our efforts to establish a blood test for

Diagnostic blood tests

lung cancer. We have met with the FDA to present our plans for the test’s validation and are working on

Prostate Cancer Moon Shot

meeting the agency’s requirements for such a study.

To date, more than 5,000 participants have enrolled in the study.

As we prepare for FDA approval of this test, we are placing substantial emphasis on its clinical implementation by developing effective modalities to screen for lung cancer. For the highest-risk group, our

Proteomics Lung Cancer Moon Shot

Pancreatic Cancer Moon Shot

approach combines CT screening and a blood test.

For those at intermediate risk, the strategy involves a

current therapy based on folfirinox, a chemotherapy

blood test first, followed by CT screening if that blood

regimen for treatment of advanced pancreatic cancer.

test is positive, with the goal of catching as many

We have identified a major enzyme in tumor tissue that

cases of early-stage lung cancer as possible while

activates a previously inactive drug in folfirinox, thereby

saving patients and the broader health care industry

potentiating response to this treatment.

innumerable time and money in the process.

In prostate cancer, we have identified and are now

26

Last year, we expanded the proteomic platform’s

testing several early detection blood biomarkers

involvement to additional cancer types in the Moon

that can help us predict the likelihood of prostate

Shots ProgramTM, particularly those with a critical

cancer being aggressive. In parallel, we are testing

need for diagnostics. We are pleased to report that

a novel lipidomics-based model for the drivers

we have made significant progress in validating a

of early aggressive prostate cancer. Finally, we

blood test for the early detection of pancreatic cancer

identified plasma biomarkers in patients undergoing

in the preclinical setting. Another important finding

active surveillance for prostate cancer. These

pertaining to pancreatic cancer is the discovery and

accomplishments would not be possible without

validation of a marker predictive of response to the

donor support, for which we are grateful.

LUNG CANCER MOON SHOT Program Leaders: John Heymach, M.D., Ph.D.; Jack Roth, M.D.; Stephen Swisher, M.D.

Daniel Gomez, M.D.

Lung cancer is the leading cause of cancer mortality

In 2016, we developed a training program, Changing

worldwide, and smoking contributes to upwards of

Tides, to establish a national standard for certified

80% of lung cancer deaths. The Lung Cancer Moon

tobacco treatment specialists. The goal is to

Shot™ combats this disease with a multi-pronged

disseminate MD Anderson-level expertise across

approach — helping to prevent young people from

the country. Thanks to your generosity, we began

starting to smoke; helping those who currently smoke

training for the program in August 2017 and expect

to quit; detecting lung cancer early when it’s treatable;

it to reach up to 43 health care providers, generating

and effectively treating it after malignancy has

more than 1,000 hours of continuing education. We

advanced from its early phases.

want to prepare health care professionals to deliver high-intensity, evidence-based, cognitive-behavioral

A Smoking Prevention Interactive Experience (ASPIRE)

treatment for nicotine dependence — just like

is an interactive program designed to reduce risk of

the Tobacco Treatment Program offered onsite at

tobacco use among adolescents. Last year, donor

MD Anderson. Additionally, four novel Moon Shot

support helped retool ASPIRE, modernizing both the

clinical trials aim to improve delivery of quit methods

content and functionality of the program, which you

and customize treatment for nicotine addiction —

can view at mdanderson.org/aspire.

assigning each participant to the intervention most likely to work based on factors that predict treatment

27

response (behavioral, genetic and neurobiological).

several research disciplines to improve treatment

These trials are exceeding recruitment goals, and

options for all lung cancer types. The project goal is to

results are expected to change clinical practice for

find cancer-driving mutations for every subset of lung

smoking cessation.

cancer — including NSCLC and those seen in only 1 or 2% of lung cancer patients. The GEMINI database

On the detection front, oncologists typically rely on

has collected detailed molecular information on more

X-ray, CT scan and/or tissue biopsy to detect lung cancer

than 4,000 lung cancer patients over the past three

in its early stages. We need to eliminate these expensive,

years. The project supported the first randomized

invasive options while maintaining the ability to detect

lung cancer clinical trial to test the hypothesis that

the disease at a time when it is most treatable.

aggressive treatment of residual metastatic disease

To this end, we have opened an international

using surgery and/or radiation (local consolidative

clinical trial focused on detecting lung cancer

therapy, or LCT) after chemotherapy could benefit

in heavy smokers using a blood test (developed

patients with limited metastatic disease. The

through our proteomics platform) and CT imaging.

benefits were so significant that the clinical trial

The goal is to show that this cheaper, safer diagnosis

was discontinued early by the data safety review

modality is as, or more, effective at detecting

board due to early

cancer than standard methods. Recent validation

efficacy. In the past

studies have confirmed that the blood test detects

year, we have built

approximately 60% of lung cancer in patients showing

on this finding by

no signs of cancer whatsoever. With your philanthropic

combining LCT with

support, the trial already has enrolled 1,450 of the

immunotherapy and

expected 10,000 patients in sites around the world.

targeted therapies, such as those that inhibit epithelial

This study established LCT as a potential standard-of-care treatment option for a subset of lung cancer patients previously offered only chemotherapy.

growth factor receptors. Clinical trials testing these Standard-of-care practices for non-small cell lung

new therapeutic combinations are currently ongoing,

cancer (NSCLC) benefit only 50% of patients with

with early results expected in 2018. Your generosity is

NSCLC, at best. The Genomic Marker-Guided Therapy

making this possible.

Initiative (GEMINI) unites lung cancer experts across

“There’s no place where the people doing the research and the people in the clinic treating patients are working together any more closely.”

— John Heymach, M.D., Ph.D.

28

PANCREATIC CANCER MOON SHOT

Program Leaders: Anirban Maitra, M.B.B.S.; Robert A. Wolff, M.D.; Matthew Katz, M.D.

This past year, with your support, the Pancreatic

have not spread past the pancreas. Each trial will be

Cancer Moon Shot™ team has made progress both

accompanied by extensive blood- and tissue-based

in the clinic and in the laboratory in our efforts to

analyses to unravel the underpinnings of response

diagnose patients earlier, increase survival after

and resistance to particular treatments.

surgical tumor removal and provide new therapies for In addition, we are collaborating with the Institute

this disease.

for Applied Cancer Science and the Center for CoMany pancreatic cancer patients with localized disease

Clinical Trials to develop targeted therapies that

will have their tumor resected (surgically removed).

inhibit recurrently abnormal genes and pathways in

Patients will live even longer, MD Anderson has

pancreatic cancer, including KRAS, which is mutated

The median overall survival for pancreatic cancer patients who successfully complete neoadjuvant therapy and surgical resection at MD Anderson is nearly double the national average.

shown, if they undergo

in as many as 95% of pancreatic cancer cases. These

neoadjuvant therapy

therapies have been shown to be highly effective

(i.e., chemotherapy with

in multiple pancreatic cancer preclinical models.

or without radiation

Several therapies will soon enter Phase I clinical trials

before surgery). Our

for pancreatic cancer, including IACS-10759, which is

goal is to evaluate novel

currently being used in an ongoing Phase I trial for

neoadjuvant treatments,

acute myeloid leukemia (for more on this trial, see

including immunotherapy,

AML-MDS Moon Shot report on page 11).

and enhance resectability and survival in our patients. This coming year, we will conduct a series

Additionally, our team is aggressively determining how

of clinical trials focused on patients whose cancers

immunotherapy can become a viable treatment option

29

for pancreatic cancer. We have successfully isolated T

sophisticated imaging techniques to pinpoint the

cells from patients, expanded them in the laboratory

location of the disease so that we can manage it

and then re-injected large volumes of these powerful

appropriately. To address this, we’re developing an

immune cells back into patients to more effectively

image processing method called enhancement pattern

fight their tumors. A new clinical trial is currently

mapping that enables detection of small-volume

enrolling patients to determine if this approach will

pancreatic tumors by amplifying abnormal signals that

generate a significant favorable response.

are usually undetectable.

Pancreatic biopsies are challenging and potentially

The chance that a healthy adult in the general

risky, but they are of extreme importance for

population will develop pancreatic cancer is

determining accurate diagnoses and prognoses for

approximately one in 10,000. However, individuals with

patients. Our novel liquid biopsy program enables

an inherited predisposition to this malignancy present

the complete genomic characterization of every

a unique opportunity for screening and early diagnosis

patient’s tumor using only a single vial of blood. This

at an asymptomatic stage. To offer this service to

technology places us in a unique position to “match”

such individuals, we’ve established Houston’s first

patients to the best trial without requiring them to

Pancreatic Cancer High-Risk Clinic, which will advise

undergo invasive tissue biopsies. This personalized

families touched by this disease, and track the

program operates in collaboration with the APOLLO

detection and progression of their disease through

platform, which means the information collected from

serial screening studies.

this study will guide drug development and allow clinicians to track a patient’s response to therapy.

We are incredibly grateful for your support, which allows us to work towards our ultimate goal of

Once a sensitive and specific blood test is available for detecting pancreatic cancer early, we’ll need

Dr. Wolff and colleagues discuss treatment strategies.

30

drastically reducing mortality from pancreatic cancer.

PROSTATE CANCER MOON SHOT Program Leaders: Christopher Logothetis, M.D.; Filippo Giancotti, M.D., Ph.D.

The leadership of the Prostate Cancer Moon ShotTM

paradigm increases effectiveness and reduces the

has prioritized projects with potential for immediate

toxicity of therapy. We are awaiting sufficient follow-up

impact on patient care. Thanks to your support,

and analysis of the data.

we have made advances in understanding why immunotherapy has not worked well in prostate

The DynAMo trial allocates patients to the most

cancer, and we are seeing promising clinical results

appropriate combination therapy based on their

in testing ways to overcome immunotherapy’s

responses to maximal hormonal therapies.

limitations. We have performed studies to classify prostate cancer into molecularly defined therapeutically relevant subgroups. We have deployed a liquid biopsy strategy that will minimize

This study is the first to take into account the heterogeneity of prostate cancer biology.

the necessity for invasive core biopsies. These

It seeks to efficiently associate marker signatures

advances have allowed us to transition from a single-

to drug response with distinct action mechanisms

agent therapy strategy to more effective combinations

that will guide future treatment strategies and the

of treatments guided by markers.

development of novel therapies within biologically informed clinical trials. Specifically, based on our

Prostate cancer is notoriously resistant to

previous studies in the clinic and in the laboratory,

immunotherapy. Based on our observations, the

men who have aggressive prostate cancers have

combined immunotherapy studies will determine if

combination chemotherapy added to the hormonal

we can overcome the limited effectiveness of single-

treatment, while men with less aggressive disease are

agent immune checkpoint inhibition with a combined

randomized to the addition of immunotherapy. As of

immune checkpoint blockade. This has evolved

now, we have 89 patients enrolled on the DynAMo

from the discovery of new immune targets to clinical

clinical trial.

applications with promising results within 18 months.

We are immensely grateful for having the philanthropic We have completed the first “intent-to-cure� clinical

support to take important steps toward the conquest

trial for prostate cancer with androgen ablation (to

of this deadly disease. Without this generous funding,

reduce levels of the male hormone that fuels most

none of these advances would be possible. On behalf

prostate cancers) for selected men with early but high-

of our patients and investigators, thank you for your

risk prostate cancer. This will determine if a curative

trust in our research.

31

COLORECTAL CANCER MOON SHOT Program Leaders: Ernest Hawk, M.D.; Scott Kopetz, M.D., Ph.D.;

Amjad Talukder, Ph.D., instructor, and

Stanley Hamilton, M.D.

Greg Lizee, Ph.D., associate professor

MD Anderson’s Colorectal Cancer Moon Shot™ has

increasing in this population. In collaboration with

made substantial progress in the past year against the

the proteomics platform, we have developed

third most commonly diagnosed malignancy in both

a blood test intended to allow primary care

men and women in the U.S. Our team is focused on

doctors to screen patients for colorectal cancer

three major areas: biomarker development for early

and polyps that lead to it. This test detects

detection, molecular subtype identification to more

biomarkers — tiny indicators of colorectal polyps/

effectively treat patients and personalized vaccine

cancers — and will allow for blood-based screening

development to harness the body's immune system to

of younger patients and more targeted use of

fight the disease.

colonoscopies for diagnosis in such screen-positive individuals. For patients who have residual cancer

32

Colonoscopies are largely effective at preventing

that is nearly undetectable after curative colorectal

colon cancer. Unfortunately, their effectiveness as

surgery, we are planning clinical trials that will also

screening tools at the population level has been

use blood-based biomarkers as surveillance tools.

limited because they are expensive, invasive and

Our approach offers a “liquid biopsy” strategy for

operator-dependent and require significant planning.

earlier detection to better stratify patients for either

Because of this, colonoscopies are not always done

continued surveillance or additional treatment. For

as frequently as recommended. Furthermore, they

example, immunotherapy might be given in response

are not widely available throughout the world, nor are

to a positive liquid biopsy to prevent cancer from

younger patients currently recommended to receive

spreading to the lung — a common site of colorectal

screening, in spite of colorectal cancer incidence

cancer metastasis. Validation studies of liquid biopsy

methods are ongoing and include analysis of many thousands of patients in the U.S. and Europe.

On the treatment side, scientists have observed that

We are developing a test that will help identify patients’ tumor subtypes and steer them into appropriate clinical trials.

colorectal cancers behave differently in different

On the immunotherapy front, our team completed

people. Our investigators helped identify four distinct

a pilot study of personalized vaccines that are built

colorectal cancer molecular subtypes. We are now

by molecularly defining a patient's tumor. This

strategically positioned to better understand the

study is demonstrating promising results and is

behaviors of tumors based on such molecular

moving into a new phase in which the vaccines are

subtypes. This will allow for more personalized

paired with immune checkpoint inhibitors. These

therapeutic approaches based on molecular

immunotherapies help make cancer cells visible to

categorizations, rather than treating colon cancer

immune system cells that are designed to eliminate

with a more traditional “one-size-fits-all� approach.

the tumor.

We demonstrated that classification can be useful in understanding more aggressive or more slowly

Thanks to the generosity of our donors, the Colorectal

growing disease subtypes. Our team has also

Cancer Moon Shot investigators are leading efforts

identified how the immune system behaves differently

to reduce the incidence of colorectal cancer and

depending on the molecular subtype. This knowledge

providing meaningful improvement in patient survival.

led to a series of clinical trials that target specific susceptibilities within these four distinct subgroups.

33

“Our obligations are unwavering and are not subject to the shifting strategic priorities common to the pharmaceutical industry. Our stakeholders are the patients and they deserve nothing less than our daily, passionate commitment to the development of innovative therapies.”

— Carlo Toniatti, M.D., Ph.D.

ORBIT

Program Leaders: Carlo Toniatti, M.D.; Ph.D., Jeffrey Molldrem, M.D.; Michael Curran, Ph.D.

The Oncology Research for Biologics and Immunotherapy

single agent and combination therapy. Phase II clinical

Translation (ORBIT) platform is dedicated to the discovery

trials are expected to begin in 2018.

and development of anti-cancer monoclonal antibodies (mAbs) — molecules that selectively recognize specific

Another advanced program in the immune checkpoint

proteins expressed on a cell’s surface. Our goal is to

space involves an mAb that can increase T cell-

effectively guide, accelerate and execute the translation

mediated anti-tumor immune responses and synergize

of novel discoveries into anti-cancer therapeutic mAbs.

with other immunotherapies in preclinical models.

ORBIT leaders feel this mAb has a high likelihood of

ORBIT is currently invested in two major areas:

becoming a safe and effective drug. We intend to find a

immune-checkpoint and T cell receptor (TCR)-

partner to start large-scale manufacturing of this mAb

like mAbs.

during 2018 with intent to enter the clinic in late 2019.

Immune-checkpoint mAbs can be used to bypass the

T cell receptor-like antibodies are a novel class of

immuno-suppressive properties of cancers and trigger

antibodies that mimic the receptor used by T cells to

a strong immune response against tumors. This class of

recognize specific targets on cancer cells and kill them.

mAbs represents the basis for the recent renaissance of

They combine the selectivity of TCRs with the strength,

cancer immunotherapy, which is producing spectacular

flexibility and pharmacologic properties of mAbs. The

results in the clinic, albeit only in a small percentage of

first ORBIT TCR-like antibody that will enter the clinic

patients and only in some cancer types. Our goal is to

is h8F4, an mAb that specifically targets and kills AML

develop novel immune checkpoint antibodies that can

cells in patients who express the PR1/HLA-A2 complex

provide a therapeutic benefit to patients that do not

on the surface of cancer cells (about 40% of the total

respond to existing immunotherapies.

AML patient population). We reached a co-development agreement with Astellas Pharma for this drug, and the

The first proprietary immune checkpoint mAb

Phase I trial of

developed at MD Anderson was an anti-OX40 agonist

this first-in-class

monoclonal antibody, which targets a protein present

mAb is projected

on the surface of T cells, thereby stimulating their anti-

to launch during

cancer activity. We entered a collaborative licensing

the first quarter

agreement with GlaxoSmithKline to co-develop this

of 2018. This is a testament to the quality of work and

mAb, the clinical development of which started in late

complexity of operations only possible at MD Anderson,

2015 and has progressed throughout 2017. Trials for

thanks to the support of our generous donors.

this drug are currently in the late stage of Phase I as

34

This will represent the only example in the world of an mAb entirely developed from target identification to Phase Ib proof-of-concept trial within an academic institution.

IMMUNOTHERAPY Program Leaders: James Allison, Ph.D.; Patrick Hwu, M.D.; Padmanee Sharma, M.D., Ph.D.

Immunotherapy is one of the newest and most

than 170 patients with AML who were undergoing

promising treatment approaches in the fight against

immunotherapy on clinical trials. The trials are showing

cancer, and one in which MD Anderson is leading the

encouraging efficacy by adding immunotherapy

way. Cancer immunotherapy has taken decades to bring

agents involving PD-1 antibodies to standard-of-

to fruition, and the immunotherapy platform has been

care hypomethylating agents, showing a doubling

the leader in bringing immunotherapy to the forefront

of response rate and improved overall survival in

as a potent weapon against cancer. Our program

frontline and relapsed AML, as well as high-risk MDS.

encompasses highly integrative basic science studies,

The immunotherapy platform is evaluating pre- and

translational research and clinical trials.

post-treatment patient samples using single-cell analyses, CyTOF and other next-generation sequencing

The strength of the immunotherapy platform is its ability to adapt based on what we learn from our clinical trials.

As we continue to

technologies. We are the first group to perform such a

expand the number

detailed analysis of ongoing clinical trials with immune

of trials, patients and

checkpoint inhibitors in AML and MDS.

samples with which we work, we are constantly

We continue to work with Moon Shots teams to bring

incorporating the newest technologies to streamline

the most advanced immunotherapies to bear on

our analyses of longitudinal samples from trials.

specific tumor types and integrate cutting-edge basic

For example, we have developed newer panels and

immunology with novel trials to gain information for

incorporated single-cell mass cytometric analyses

the treatment and eradication of cancer. We thank

for a deeper understanding of T cells and other

our generous donors for their support, without which

immune cells, which have a major impact on cancer

none of this would be possible.

progression.

More than 63,000 blood and From our collaboration with the department of

tissue samples processed, covering

Leukemia and the AML-MDS Moon Shot™, we

a broad range of tumor types across

collected bone marrow and blood samples from more

18 departments from 113 clinical trials

35

GLIOBLASTOMA MOON SHOT Program Leaders: Amy Heimberger, M.D.; Frederick Lang, Jr., M.D.; John de Groot, M.D. Uncovering better treatments for glioblastoma, the most common brain tumor, is the goal of MD Anderson’s Glioblastoma Moon Shot™. Current standard regimens include surgery, radiation and

A second immunotherapy approach in

chemotherapy — harsh treatments that often mean

preclinical studies focuses on chimeric antigen

severe side effects for patients. Nevertheless, we are

receptor (CAR) T cells. Amy Heimberger,

making progress by developing more effective, patient-

M.D., professor of Neurosurgery, devised a

friendly approaches.

method to reduce the amount of time needed to produce these cells from 28 days to 14.

One promising area for treating glioblastomas

Halving the time for CAR T cell production is

is immunotherapy. Elizabeth Shpall, M.D., and

a huge win for patients who need access to

Katy Rezvani, M.D., Ph.D., professors of Stem Cell

therapy quickly.

Transplantation and Cellular Therapy, opened an exciting clinical trial targeting cytomegalovirus (CMV).

Evidence indicates that most glioblastomas exhibit

type of brain cancer, a 15% response rate is incredibly

CMV-derived viral proteins. MD Anderson researchers

exciting. Second, the team noticed that the presence of

have crafted CMV-specific T cells from the peripheral

a foreign virus elicited a simultaneous immune reaction,

blood of glioblastoma patients that detect, find and

suggesting viral and immunotherapy combinations

kill the CMV-protein-producing tumor cells. Since the

may be an effective approach. In light of this, a new

trial opened, the six enrolled patients have shown no

clinical trial has opened teaming Delta-24-RGD with the

adverse effects stemming from the treatment. Once

immunotherapy pembrolizumab. Patients enrolled in

the safety studies conclude, the next step is to test the

the trial are already showing encouraging results.

tumor-killing potency of this approach in patients.

Lastly, by leveraging the extensive molecular profiling Viral therapy could be the next frontier in glioblastoma

efforts of MD Anderson’s APOLLO platform, we have

treatment. MD Anderson’s Delta 24-RGD is a cancer-

treated numerous patients in clinical trials by identifying

killing therapy modified from the common cold virus.

subgroups who are eligible for targeted therapies. For

Developed by Juan Fueyo, M.D., and Candelaria

example, in one of these cohorts, every patient has

Gomez-Manzano, M.D., professor and associate

three mutations on a particular chromosome and may

professor of Neuro-Oncology, respectively, the virus

respond to a drug that targets these mutations. Although

selectively infects and kills glioblastoma cells when

this is a small patient subset, molecular database surveys

delivered directly to the tumor. Then, the Delta- 24-RGD

have identified 10

replicates within the dying tumor cell before bursting

more people who

out and flooding the tumor with copies of itself,

may be eligible for

essentially releasing a new therapy wave.

this therapy.

In a Delta-24-RGD clinical trial led by Frederick Lang,

With heartfelt appreciation, we thank you for

M.D., professor of Neurosurgery, our team made

supporting our efforts in improving the disease

two critical discoveries. First, 15% of patients treated

outcomes of patients with glioblastoma.

demonstrated a beneficial therapeutic effect. For any 36

Those 10 people will be given a better chance to beat cancer because of the unique, collaborative structure of the Moon Shots ProgramTM.

For more updates, visit: cancermoonshots.org

CANCERMOONSHOTS.ORG